Powerful new autoradiographic and enzyme histochemical methods for tracing central neural connections using the physiological processes of anterograde and retrograde axoplasmic transport have been developed in the last 5 years. In addition, immunohistochemical techniques may now be used to localize certain biochemically defined cell systems within the brain. Each of these methods have been applied in our laboratory to study the connections of the limbic system and hypothalamus, regions thought to be involved in the central regulation of the autonomic nervous system and the endocrine system. Detailed autoradiographic studies of the hippocampus, septum and preoptic area in the rat, for example, have (a) clarified the origins of different components of the fornix system, (b) demonstrated the paths taken by visual information to the hypophysiotrophic area of the hypothalamus, and (c) revealed the efferent connections of the preoptic area to widespread regions of the brain including, among others, the olfactory bulb, the substantia nigra, and the locus coeruleus. The research proposed here is an extension of these studies and aimed at determining (1) the efferent connections of the hypothalamus, especially to the vagal complex and spinal cord, and their precise cells of origin, (2) the sources of neural inputs to the limbic system, and the pathways through which the limbic system influences bulbar and spinal autonomic effector centers, and (3) the extent to which limbic and hypothalamic connections in the primate brain resemble those demonstrated in lower species like the rat. Specifically, the efferent connections of the hippocampus, mammillary complex and anterior thalamic nuclei will be studied autoradiographically in the monkey. Hippocampal, hypothalamic, and midbrain connections will be studied autoradiographically, immunohistochemically, and with horseradish peroxidase histochemistry in the rat.